Surgical Site Infections

a a,b,
Pang Y. Young, MD , Rachel G. Khadaroo, MD, PhD, FRCSC *

KEYWORDS
 Surgical site infection  Surgical wound infections  Antibiotic prophylaxis
 Infection control  Postoperative complication

KEY POINTS
 Surgical site infections (SSIs) are major contributors to patient morbidity and mortality in
hospital settings.
 Risk for SSI is multifactorial and includes modifiable and nonmodifiable factors.
 Basic and clinical research has expanded evidence-based guidelines for SSI prevention.
 SSIs are increasingly used as outcome and surrogate measures for examining the quality
of surgical care.
 A culture of safety and quality is an important element to reducing SSI.

INTRODUCTION

Surgical site infections (SSIs) have played a major role in the evolution of medical care
throughout history. Wound complications contributed significantly to the historical sur-
gical mortality rates before the development of Listers aseptic approach in the nine-
teenth century.1 The impact of the antiseptic/aseptic techniques was readily apparent
in its adaptation to battlefield medicine. During the Civil War in America, surgeons
routinely operated bare-handed, with wound suppuration considered to be a beneficial
aspect of wound healing.2 With the gradual acceptance of the principles of antisepsis,
and the usage of sterile dressings and aseptic surgical technique, there was a dramatic
reduction in mortality from wounds to 7.4% in the Spanish-American War.3
Despite nearly 2 centuries of medical progress, the management of surgical infec-
tion remains a pressing concern, and SSIs continue to be a leading component of
nosocomial morbidity and mortality. In this article, the epidemiology, pathogenesis,

Disclosures: No conflicts of interest to disclose.

a
Division of General Surgery, Department of Surgery, Faculty of Medicine and Dentistry,
University of Alberta, 8440112 Street Northwest, Edmonton, Alberta T6G 2B7, Canada;
b
Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta,
8440112 Street Northwest, Edmonton, Alberta T6G 2B7, Canada
* Corresponding author. 2D Walter C. Mackenzie Health Sciences Centre, 8440112 Street
Northwest, Edmonton, Alberta T6G 2R7, Canada.
E-mail address: khadaroo@ualberta.ca

Surg Clin N Am 94 (2014) 12451264

http://dx.doi.org/10.1016/j.suc.2014.08.008 surgical.theclinics.com
0039-6109/14/$ see front matter 2014 Elsevier Inc. All rights reserved.
1246 Young & Khadaroo

risk factors, and approach to prevention of SSIs are reviewed. This review highlights
the multifaceted and multidisciplinary approach to management of SSIs, which are
a critical aspect of infection control outcomes.

DEFINITIONS

To assist with appropriate surveillance of SSIs, establishing clear definitions for cases
of SSIs was critical. The Centers for Disease Control and Prevention (CDC) established
the National Healthcare Safety Network (NHSN) to monitor quality control measures,
including SSIs, and has defined widely used definitions for SSI (Box 1).4 SSI are clas-
sified based on the depth of involvement of the infection, which may be confined to the
skin and subcutaneous tissues (superficial incisional SSI), involve the deep soft tissue,
such as the fascial and muscular layers (deep incisional SSI), or extend further beyond
these anatomic boundaries (organ/space SSI) (Fig. 1).5 Incisional SSIs are further sub-
divided into primary and secondary for cases with more than one incision. For
instance, a primary incisional SSI involves the primary incision (eg, chest incision for
coronary artery bypass grafting), and a secondary incisional SSI involves secondary
incisions (eg, leg incision for donor site in coronary artery bypass grafting).

EPIDEMIOLOGY

Recognizing the historical context of surgical infection can highlight the gains that
have been made over the past few centuries. Before the antisepsis era, the risk of sur-
gery was exceedingly high due to the enormous rates of surgical infection. Com-
pounded by the absence of the effective anesthesia, early surgical procedures had
limited success compared with the modern era. Acknowledgment of the aseptic
approach made a significant impact on outcomes. The simple introduction of hand
washing by Semmelweis resulted in a decrease in mortality due to puerperal sepsis
from 12% to 2%.6
The development of multiple aspects of modern surgical care has led to significant
improvements in the historical context described. Nevertheless, SSIs remain a
frequent postoperative complication, developing in 3% to 20% of surgical proce-
dures.7 The rate of SSI is highly variable depending on the specific operative proce-
dure, with rates that can be even higher depending on the number of risk factors
present.
There is a substantial impact of SSI on both morbidity and mortality. However,
establishing the exact impact of SSI is difficult because of the dependence on accu-
racy of reporting and the variability of patient follow-up. In the 1980s, it was observed
that SSI led to a 10-day increase in hospital length of stay.8 Even a decade later,
another study reported persistent delayed discharge from hospital and increased
requirement for post-discharge care.9 In a study of 288,906 patients, in-hospital mor-
tality for the patients with SSIs was 14.5% versus 1.8% of patients with no SSI. SSIs
are estimated to be responsible for more than 8000 deaths annually in the United
States.7 SSIs may be of even greater consequence in developing countries, because
surveillance rates of SSI in a study conducted by the International Nosocomial Infec-
tion Control Consortium were higher for most surgical procedures compared with
CDC-NHSN rates.10

RISK FACTORS FOR SURGICAL SITE INFECTION

From a general perspective, the microbes responsible for infection of surgical wounds
originate from either the surrounding skin or associated structures that are contiguous
 Surgical Site Infections 1247

Box 1
Centers for Disease Control and PreventionNational Healthcare Safety Network definitions
for surgical site infections

Superficial incisional surgical site infection

Infection occurs within 30 days after the operative procedure and
Involves only skin and subcutaneous tissue of the incision and
Patient has at least 1 of the following:
a. Purulent drainage from the superficial incision
b. Organisms isolated from an aseptically obtained culture of fluid or tissue from the
superficial incision
c. At least 1 of the following signs or symptoms of infection: pain or tenderness, localized
swelling, redness, or heat, and superficial incision is deliberately opened by surgeon and
is culture positive or not cultured. A culture-negative finding does not meet this criterion
d. Diagnosis of superficial incisional SSI by the surgeon or attending physician
Deep incisional surgical site infection
Infection occurs within 30 days after the operative procedure if no implant is left in place or
within 1 year if implant is in place and the infection appears to be related to the operative
procedure and
Involves deep soft tissues (eg, fascial and muscle layers) of the incision and
Patient has at least 1 of the following:
a. Purulent drainage from the deep incision but not from the organ/space component of the
surgical site
b. A deep incision spontaneously dehisces or is deliberately opened by a surgeon and is
culture-positive or not cultured when the patient has at least 1 of the following signs or
symptoms: fever (>38 C) or localized pain or tenderness. A culture-negative finding does
not meet this criterion
c. An abscess or other evidence of infection involving the deep incision is found on direct
examination, during reoperation, or by histopathologic or radiologic examination
d. Diagnosis of a deep incisional SSI by a surgeon or attending physician
Organ/space surgical site infection
Infection occurs within 30 days after the operative procedure if no implant is left in place or
within 1 year if implant is in place and the infection appears to be related to the operative
procedure and infection involves any part of the body, excluding the skin incision, fascia, or
muscle layers, that is opened or manipulated during the operative procedure and
Patient has at least 1 of the following:
a. Purulent drainage from a drain that is placed through a stab wound into the organ/space
b. Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space
c. An abscess or other evidence of infection involving the organ/space that is found on direct
examination, during reoperation, or by histopathologic or radiologic examination
d. Diagnosis of an organ/space SSI by a surgeon or attending physician.

From Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-
associated infection and criteria for specific types of infections in the acute care setting. Am
J Infect Control 2008;36:3134; with permission.
1248 Young & Khadaroo

Fig. 1. Schematic for CDC classification of surgical site infection. (From Horan TC, Gaynes RP,
Martone WJ, et al. CDC definitions of nosocomial surgical site infections, 1992: a modifica-
tion of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol 1992;
13(10):6068.)

with the regions of the surgical procedure. The logical extension of this principle is that
the risk of wound contamination and subsequent SSI depends on location, the nature
of the surgical wound/incision, and the procedure performed. The CDC wound clas-
sification system defines wound class based on risk and is divided into 4 categories:
clean, clean-contaminated, contaminated, and dirty (Table 1).5 With clean wounds,
the expected risk is from microbes located directly on the surface of the skin, or intro-
duced from the external environment. With increasing wound class, there is increased
exposure to microorganisms that are present on internal structures of the body, such
as epithelial surfaces of the gastrointestinal tract and genitourinary tract. In the early
epidemiologic studies, the SSI rate increased with wound class (I, 2.1%; II, 3.3%;
III, 6.4%; IV, 7.1%).11
Appropriate risk stratification for SSI cannot be limited to the wound alone. There
are a variety of patient-related factors and perioperative factors that can significantly
affect the risk of SSI in a surgical patient (Box 2). One system of risk stratification is the
National Nosocomial Infection Surveillance (NNIS) System risk score, based on 3 fac-
tors. These factors are (1) an American Society of Anesthesiology preoperative
assessment score of greater than or equal to 3; (2) an operation with a wound classi-
fication as contaminated or dirty; and (3) an operation longer than the 75th percentile in
duration for the specific procedure.11 In the original development of the NNIS risk
score, each additional risk factor resulted in increasing rates of SSI, even within the
same traditional wound class. In the most recent publication of aggregate data from
the NHSN SSI surveillance system, the effects of risk factors remain apparent
(Table 2), with escalating SSI rates with the number of risk factors. The NNIS score
has been further modified to account for some specific instances of laparoscopic
cases, as the risk for SSI can be lower.
The risk factors identified in the NNIS risk scoring system are useful from surveil-
lance and monitoring perspectives. However, prevention requires identification of
 Surgical Site Infections 1249

Table 1
Surgical wound classification

Class Type Description

I Clean An uninfected operative wound in which no inflammation is
encountered and the respiratory, alimentary, genital, or uninfected
urinary tract is not entered. In addition, clean wounds are primarily
closed and, if necessary, drained with closed drainage. Operative
incisional wounds that follow nonpenetrating (blunt) trauma
should be included in this category if they meet the criteria.
II Clean An operative wound in which the respiratory, alimentary, genital, or
contaminated urinary tracts are entered under controlled conditions and without
unusual contamination. Specifically, operations involving the
biliary tract, appendix, vagina, and oropharynx are included in this
category, provided no evidence of infection or major break in
technique is encountered.
III Contaminated Open, fresh, accidental wounds. In addition, operations with major
breaks in sterile technique (eg, open cardiac massage) or gross
spillage from the gastrointestinal tract, and incisions in which
acute, nonpurulent inflammation is encountered are included in
this category.
IV Dirtyinfected Old traumatic wounds with retained devitalized tissue and those that
involve existing clinical infection or perforated viscera. This
definition suggests that the organisms causing postoperative
infection were present in the operative field before the operation.

From Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site infection,
1999. Am J Infect Control 1999;27:109; with permission.

risk factors that are more readily modifiable than those listed in the NNIS scoring sys-
tem. An approach to the risk factors of SSIs can be categorized into a schematic of
microbial factors, patient factors, and perioperative factors.

MICROBIAL FACTORS

The predominant source of microbes involved in SSIs originate from either the skin or
the surrounding tissues of the incision, or from deeper structures involved in the oper-
ative procedure (eg, enteric organisms in bowel-related surgeries). In the most recent
NHSN surveillance report on 21,100 isolates from 2009 to 2010, the most frequently
identified pathogens were, in order, Staphylococcus aureus, Coagulase-negative
Staphylococci, Escherichia coli, Enterococcus faecalis, and Pseudomonas aerugi-
nosa.12 The overall distribution of pathogens associated with SSI has changed to
some extent over the past couple decades (Table 3).1214 The proportion of gram-
negative bacilli has decreased coinciding with a relative increase in the proportion
of S aureusrelated infection. In the most recently published 2010 NHSN data, S
aureus accounted for 30.4% of SSI, up from 20% in the early 1990s. Individual insti-
tutions may have variations in the proportions of specific species, due to differences in
the volumes of various surgical specialties.
The temporal trend of significance is the substantial growth in multidrug resistance
(MDR). The most apparent example is the increase in methicillin-resistant Staphylo-
coccus aureus (MRSA).15 In a study of community hospitals in southeastern United
States, the incidence of MRSA-associated SSI increased from 12% in 2000 to 23%
in 2005.16 In the 2010 NHSN update, the proportion of SSI due to MRSA was
43.7%.12 Increases in MRSA prevalence internationally show similar temporal trends.
1250 Young & Khadaroo

Box 2
Risk factors for surgical site infection

Patient factors
Age
Nutritional status
Diabetes
Smoking
Obesity
Coexistent infections at a remote body site
Colonization with microorganisms
Altered immune response
Length of preoperative stay
Operative factors
Duration of surgical scrub
Skin antisepsis
Preoperative shaving
Preoperative skin preparation
Duration of operation
Antimicrobial prophylaxis
Operating room ventilation
Inadequate sterilization of instruments
Foreign material in the surgical site
Surgical drains
Surgical technique
Poor hemostasis
Failure to obliterate dead space
Tissue trauma

From Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site infec-
tion, 1999. Am J Infect Control 1999;27:105; with permission.

In a Japanese study of 702 isolates, methicillin resistance in S aureus isolates was

72.0%.17 Community-acquired MRSA is increasing in prevalence, with the prevalence
of nasal colonization with MRSA in the general population increasing from 0.8% to
1.5% from 20012002 to 20032004.18 Studies have attempted to clarify the relation-
ship between colonization and risk for MRSA SSI. In a study of 9006 patients in a
Pennsylvania tertiary care hospital by Kalra and colleagues,19 4.3% of patients were
positive for nasal MRSA screening; the MRSA SSI rate was 1.86% in MRSA-
screen-positive patients compared with 0.20% in MRSA-screen-negative patients.
An important aspect of the temporal changes in MDR pathogens is the significant
alteration in the pharmacodynamics of the antibiotics used to manage these infec-
tions. Several studies have shown an upward shift in minimal inhibitory concentration
(MIC) of vancomycin in clinically isolated strains of MRSA, described as MIC creep.
 Surgical Site Infections 1251

Table 2
Surgical site infection rates, based on risk index for various surgical procedures

Risk Index (%)

Procedure 0 1 2 3
CABG with chest and donor incision 0.35 2.55 4.26 8.49
Breast surgery 0.95 2.95 6.46
Colon surgery 3.99 5.59 7.06 9.47
Gallbladder surgery (inpatient) 0.23 0.61 1.72
Herniorrhaphy (inpatient) 0.74 2.42 5.25
Rectal surgery 3.47 7.99 26.67
Small bowel surgery 3.44 6.75
Thoracic surgery 0.76 2.04

Abbreviation: CABG, coronary artery bypass grafting.

Data from Edwards JR, Peterson KD, Mu Y, et al. National Healthcare Safety Network (NHSN)
report: data summary for 2006 through 2008, issued December 2009. Am J Infect Control
2009;37:783805.

During a period between 2000 and 2004, Wang and colleagues20 reported on 6003
clinical isolates, showing a large significant increase in the proportion of isolates
with vancomycin MIC of 1 mg/L from 19.9% to 70.4%. In a 5-year period between
2001 and 2005, Steinkraus and colleagues21 reported a significant increase in the
MIC of vancomycin, oxacillin, and linezolid in 662 isolates collected over the 5-year
period. For vancomycin, in particular, there was a significant shift in proportion of iso-
lates with MIC 0.5 mg/L, from 46% in 2001 to 5% in 2006.
There have been conflicting data with respect to MIC creep. Several surveillance
studies from Canadian, United Kingdom, and American centers have not demon-
strated the same degree of MIC creep.2224 Additional controversy lies in the method-
ologies to represent changes in MIC. In general, these trends remain cause for
concern as higher MIC is predictive of vancomycin treatment failure in MRSA.25 In
some series, MRSA infection has been independently associated with mortality.26
Narrowing of the therapeutic window will increase the risk for adverse effects as
dosing targets are adjusted.27 Management of MRSA as a single example of antibiotic
resistance carries a significant burden of cost.

Table 3
Distribution of causative pathogenic organisms in surgical site infection, reported by the
National Healthcare Safety Network at various reporting dates

Year
Pathogen 19901996 2007 2010
S aureus 20% 30.0% 30.4%
Coagulase-negative Staphylococcus 14% 13.7% 11.7%
Enterococcus sp. 12% 11.2% 11.6%
E coli 8% 9.6% 9.4%
P aeruginosa 8% 5.6% 5.5%
Enterobacter sp 7% 4.2% 4.0%
K pneumoniae 3% 3.0% 4.0%
1214
Data from Refs.
1252 Young & Khadaroo

The concerns of antibiotic resistance are increasing as new mechanisms for multidrug
resistance are continuing to develop. For instance, New Delhi metallo-b-lactamase 1
(NDM-1) was first reported in Sweden in 2008.28 It has been increasingly identified in iso-
lates from India, Pakistan, and the United Kingdom.29 The global spread of NDM-1 is
now broad, with identification in Canada, United States, Australia, China, and
Russia.3034 The resistance mechanism was first identified in Klebsiella pneumoniae
and E coli.28 Other species of Enterobacteriaceae have now also been identified to har-
bor NDM-1, including Acinetobacter, Enterobacter, Providencia, and Raoultella. It has
been primarily identified in patients with community-acquired pneumonia, urinary tract
infections, and bacteremia.29 Nevertheless, like the spread geographically and in speci-
ation, there is significant potential impact with SSI. In one case report, Acinetobacter
baumanii expressing NDM-1 was isolated from a Dacron graft infection.35 NDM-1 is
just one example of an MDR mechanism that has spread globally in a few short years.36
A discussion on microbial factors in surgical infection can extend far beyond a dis-
cussion on cause alone. There is a growing body of research literature that suggests
that there is an important role of the host microbiome in response to disease.37 The
most well-studied interactions are within inflammatory bowel disease, which demon-
strates a clear relationship with altered microbiome composition.38,39 Understanding
of the interaction of the host microbiome with wound healing is evolving. As an
example, in an animal model of anastomotic leak, there is an association of anasto-
motic leak with specific virulence factors in P aeruginosa.40 Further research may
significantly alter the understanding of surgical infection and the interaction with mi-
crobial etiologies.

PATIENT FACTORS

Patient comorbidities can contribute significantly to the potential risk of SSIs. These
factors include age, obesity, smoking, diabetes mellitus, malnutrition, dyslipidemia,
and immunosuppression (see Box 2).41 These factors are not directly accounted for
in the NNIS classification scheme but can contribute significantly to the risk of SSI.
Identification of these risk factors with appropriate preoperative history and physical
examination is critical. The core principle for management of these patient-related
risk factors is preoperative optimization.
Because many of the patient comorbidities are nonmodifiable, there can be a sub-
stantial increase in SSI risk. Particularly in urgent or emergent situations, there may not
be an opportunity to optimize a patients comorbid status fully. The rate of SSI is ex-
pected to be much higher in emergency surgery, as opposed to elective cases, which
has been demonstrated in many studies.4143 The higher SSI rate in emergency cases
also signifies patients that are more critically ill, with greater physiologic compromise,
and expectedly, worse outcome.
Other patient-related risk factors are also often nonmodifiable in the timeline of pre-
operative planning. Although age is clearly a nonmodifiable risk factor, other comor-
bidities, such as diabetes, obesity, and immunosuppression, are not easily
reversible in a short-term time frame. Optimization of these risk factors is critical.
For diabetes, optimization of glucose control has been clearly demonstrated to
have efficacy in reduction of SSI rates.41,44,45 In the cardiac surgery literature, rates
of sternal wound infection have been shown to improve with the quality of glycemic
control.4648 Glycemic control optimization recommendations include a reduction in
serum glucose levels and a reduction in HgbA1c to less than 7.0%.45,49
Smoking results in significantly increased risk of SSI because of its effects on local
tissue perfusion. Large numbers of studies have consistently shown that smoking
 Surgical Site Infections 1253

results in at least a 2-fold increased risk of SSI.44 In one trial by Mller and col-
leagues50 of 120 patients, smoking cessation therapy resulted in a reduction of
wound-related complications from 31% to 5%. This finding has been confirmed by
additional studies, and in meta-analyses of trial data.51,52 Recommendations are for
smoking cessation at least 30 days before operation.41,44,45
For patients that have significantly elevated risk because of risk factors that cannot
be modified, additional preventative measures need to be considered and can include
the use of altered protocols for antimicrobial prophylaxis (as discussed later), or
consideration of additional risk reduction measures.

PERIOPERATIVE FACTORS

Preventative measures in the preoperative period have changed rapidly over the past
few decades. A large volume of research has established the importance of a host of
preventative measures in the operative period. Examples include skin decontamina-
tion, perioperative warming, and antimicrobial prophylaxis.41,44,45 As additional
studies have been conducted with increasing methodological rigor, from observa-
tional studies to randomized controlled trials, refinements of existing preventative
measures have further improved the efficacy of these measures. This review focuses
on areas of prevention that are the focus of significant active research or have seen
recent changes in key guidelines or recommendations.

Skin Decontamination
The use of antiseptic agents topically has long been recommended for use in skin
decontamination.5 The 2 broad classes of topical agents include chlorhexidine-
based preparations and iodophor-based agents. In addition, these agents can be
combined with isopropyl alcohol (IPA) in solution. Several studies have sought to
address potential differences in efficacy between the various available agents,
although there has been significant inconsistency of results, which have been also
been confounded by methodological differences between the studies.
In the systematic review and meta-analysis conducted by Lee and colleagues,53
chlorhexidine-based agents were found to reduce the risk of SSIs significantly, with
an adjusted risk ratio of 0.64, and result in a net cost-savings over the use of
iodophor-based agents. This analysis included 9 randomized controlled trials, but
in several of the included trials, chlorhexidine-based solutions containing IPA
were compared with povidone-iodine solutions not containing IPA, which
confounded the results of the analysis.5456 In a nonrandomized study by Swenson
and colleagues,57 there was no significant difference between chlorhexidine/IPA
and 1 of 2 forms of iodophor-based agents (povidone-iodine or iodine povacrylex
in IPA).
In the most recently published cohort study by Hakkarainen and colleagues,58 there
were no significant differences between 4 different preparations of skin antisepsis
agents (chlorhexidine/IPA, chlorhexidine, povidone-iodine, and iodine-povacrylex/
IPA) in a cohort of primarily clean-contaminated general surgical cases. In their
conclusion, there was minimal incremental benefit for chlorhexidine-based agent in
their specific subset of clean-contaminated cases. As one prospective European
study highlighted, there was no direct correlation between the residual bacterial flora
following disinfection and subsequent SSI in a variety of surgical cases,59 suggesting
that in certain surgical disciplines, the choice of skin antisepsis has less effect, partic-
ularly when the microbial cause lies in noncutaneous sources, such as enteric sources
for general surgical procedures.
1254 Young & Khadaroo

Antibiotic Prophylaxis
From a historical perspective, routine antibiotic prophylaxis was questioned for its
usefulness. With demonstrated clinical benefit in the clinical trials conducted sepa-
rately by Polk and Lopez-Mayor and Stone and colleagues,60,61 there has been
tremendous improvement in SSI as an outcome. From the outset, the development
of antibiotic prophylaxis has undoubtedly led to a clear reduction in rates of SSI.
The complexity and nuance of clinical practice guidelines has continued to become
more complex and refined.
Although there have been continual updates to the clinical practice guidelines, the
general principles of antimicrobial prophylaxis are consistent.41,6264 First, the antimi-
crobial agent should be safe. Second, an appropriate antimicrobial agent should be
selected that has a narrow spectrum of coverage for the expected relevant pathogens.
Third, antimicrobial prophylaxis should be administered in the preoperative period to
allow serum and tissue concentrations to reach appropriate levels at the time of inci-
sion. Last, the antimicrobial agent should be administered for the shortest effect
period, with appropriate discontinuation of the agent.
Clinical practice guidelines for antimicrobial prophylaxis were recently updated in
2013 in a joint publication by the American Society of Health-System Pharmacists, the
Infectious Diseases Society of America, the Surgical Infection Society, and the Society
for Healthcare Epidemiology of America.63 The revised guidelines replaced the previ-
ously published 1999 guidelines65 and highlighted several focuses including timing of
preoperative dosing, weight-based dosing, and duration of postoperative prophylaxis.
Selection of antibiotics for prophylaxis should be made with the primary consider-
ation of the spectrum of coverage required. This consideration should be made
because of the wound classification and the overall risk of infection. For example, in
clean surgical procedures, the risk of SSI is relatively low and, in several cases, anti-
microbial prophylaxis is not indicated.41 Prophylaxis is considered in specific clean
procedures where the consequence of infection is critical (eg, prosthetic implants,
cardiac pacemakers). Consideration of intrinsic patient-related factors associated
with increased risk of SSI (eg, age, malnutrition, immunosuppression) is relevant
and appropriate justification for the use of antimicrobial prophylaxis.63,65 A meta-
analysis conducted by Bowater and colleagues66 demonstrated that the relative risk
reduction was the same across wound classes.
In clean procedures, the primary coverage is for the likely Staphylococcus sp. that
will be the predominant cause. For clean-contaminated procedures, similar spectrum
of coverage for Staphylococus sp. is required, with additional coverage as needed
depending on the site of surgery. As such, first-generation and second-generation
cephalosporins remain the recommended prophylactic antibiotics for a large number
of surgical procedures.41,63,65 For contaminated and dirty wound classes, prophylaxis
is typically not indicated, because therapeutic antibiotic management is required.
Preoperative dosing of antibiotic prophylaxis is optimized to allow serum and tissue
concentrations to reach sufficient levels at the time of incision. Several studies have
studied the precise timeline for preoperative administration of prophylaxis to achieve
maximal benefit. In 1992, Classen and colleagues67 showed a decreased SSI rate
to 0.59% with administration within 2 hours of incision, compared with 3.8% for early
(224 hours before incision) and 3.3% for postoperative administration. In a cardiac
surgery study of 2048 patients, the rate of SSI was lowest in the group receiving van-
comycin prophylaxis in the window of 16 to 60 minutes before incision.68
Trends have been seen in several studies that may suggest that the window for pre-
operative antibiotics could be narrowed to 30 minutes of incision. In the Trial to
 Surgical Site Infections 1255

Reduce Antimicrobial Prophylaxis Errors (TRAPE) study of 4722 patients undergoing

cardiac, arthroplasty, or hysterectomy procedures, the effect of specific windows of
antibiotic prophylaxis (in 30-minute intervals, preceding and following incision) was
examined.69 The lowest rate of SSI was in the 30-minute window immediately before
incision. In an orthopedic study by van Kasteren and colleagues,70 1922 patients un-
dergoing hip arthroplasty were examined. The rates of SSI in the groups receiving an-
tibiotics in the 1- to 30-minute and 31- to 60-minute windows were 2.19% and 2.60%,
respectively, which was not statistically significant. Both studies reinforced that the
highest rate of SSI occurred in groups receiving antibiotics following incision. The po-
tential incremental benefit of an earlier antibiotic window is likely small and would be
difficult to detect without significantly larger sample sizes. Current guidelines empha-
size prophylaxis administration within 60 minutes of incision, or within 120 minutes for
antibiotics requiring longer infusion times.63
In the updated clinical practice guidelines, weight-based dosing is an additional
focus.63 Particularly in obese patients, studies have shown the pharmacokinetics of
antibiotic administration are significantly altered. In a 1989 study on obese patients
undergoing gastroplasty and normal-weight adults undergoing abdominal surgery,
1 g dosing of cefazolin resulted in significantly lower blood and tissue concentrations
in obese patients.71 However, 2 g dosing of cefazolin resulted in blood and tissue
levels equivalent to normal-weight patients. Guidelines recommend increased dosing
and fewer adjustments in renal impairment.63,64
Adequate redosing of antibiotics for longer operative procedures is necessary for
risk reduction. With longer procedures, serum and tissue concentrations can drop
below adequate levels, particularly in antibiotics with shorter half-lives (eg, cefazolin,
cefoxitin, gentamicin).63,72 The effect was seen even in smaller case series. In the
study by Morita and colleagues73 of 131 patients undergoing colorectal procedures,
the SSI rates in procedures longer than 4 hours were 8.5% and 26.5%, in groups
with or without redosing, respectively. In the TRAPE trial, the rate of SSI was increased
with an absence of redosing, 5.5% versus 1.8%.69 Guidelines emphasize repeated
dosing at intervals of 2 half-lives of the antibiotic used.63
Additional routes of antibiotic administration have been investigated in the past and
have been historically ruled out. Topical routes of antibiotic prophylaxis have been
considered for some time. Recent reinvestigation into topical antibiotic prophylaxis
has been most thorough in the cardiac surgery literature. Gentamicin-impregnated
sponges have been studied in several randomized controlled trials for the prevention
of sternal wounds.7477 A recent meta-analysis by Mavros and colleagues78 demon-
strated that gentamicin collagen sponges reduced the risk of deep sternal wound in-
fections, although there was significant heterogeneity among the included
randomized controlled trials. However, in a trial by Bennett-Guerrero and col-
leagues,79 no benefit was seen in a group of 602 colorectal surgery patients, with
significantly higher SSI rates in the gentamicin sponge group. Further interest is still
present in examining topical antibiotics in general surgical populations,80 but more
rigorous evidence will need to be presented before any adoption. With the recent
guidelines, there are no recommendations describing a role for topical routes of anti-
biotic administration.63

Additional Measures
Several additional measures have been investigated for implementation in the preven-
tion of SSI. In many circumstances, recommendations have been equivocal due to the
lack of evidence or the presence of often contradictory evidence. In these cases,
guidelines are directed by expert opinion and experience. Further research is
1256 Young & Khadaroo

continuing to clarify controversial issues in SSI prevention, and in some cases, causing
further controversy.
As a prime example, perioperative oxygenation was shown in 2 early trials to lead to a
reduction in SSI rates with the use of 80% oxygen intraoperatively and immediately post-
operatively.81,82 Further investigations have been mixed, with 2 prominent studies
showing negative findings for efficacy.83,84 In the PROXI trial, a large Danish randomized
controlled trial studied 1400 patients undergoing abdominal surgery, who received either
80% oxygen or 30% oxygen during and for 2 hours after surgery.83 There was no signif-
icant difference in SSI rates with increased perioperative oxygen fraction. In addition,
subsequent subgroup analysis of the PROXI study showed there was increased long-
term mortality in the high inspired oxygen group, with patients undergoing cancer sur-
gery,85 although this secondary finding of mortality difference is controversial because
of potential confounding, sample size, and lack of a convincing biological mechanism.
Several conducted meta-analyses of these trials do suggest an overall reduction of
SSI rates.8688 There is significant heterogeneity of the trials performed, with variability
of the type of surgical procedures, perioperative care, and delivery protocol for hyper-
oxia. Perioperative hyperoxia has been included in some recommendations for the
prevention of SSIs.44
Perioperative measures with considerably less controversy include perioperative
warming, hair removal, and optimization of the operating room environment. Periopera-
tive hypothermia is associated with significantly increased risk of SSI.41,89,90 With regards
to hair removal, the lowest risk of SSI has always been associated with not removing hair.
If hair needs to be removed because of interference with the procedure, then hair removal
should be done immediately before the surgery with a clipper rather a razor.41,44,91,92
The development of further preventative measures will require additional research,
combining both basic and clinical research. Even with the existing measures, there
continue to be areas that are controversial due to the conflicting data available. As
baseline SSI rates decline with improving standard of care, identification of additional
methods of prevention will continue to become more challenging.

MAJOR LIMITATIONS IN PREVENTION

In an ideal scenario, primary prevention is completely effective and the burden of SSI-
related morbidity is reduced to 0%. As described in later discussion, the relationship
between compliance with evidence-based guidelines and SSI outcomes is imperfect.
With the risk inherent with nonmodifiable risk factors, there will likely be a minimum
prevalence that cannot be entirely eliminated. In addition, with the development of
numerous evidence-based guidelines, there continue to be hurdles with implementa-
tion and translation of these guidelines to practice.
In several jurisdictions, there is incomplete compliance with guidelines, even when
associated with checklists, pathways, and packages. Compliance itself is a multifacto-
rial issue that can be limited by a host of factors. Compliance can be limited by lack of
awareness of guidelines by members of the multidisciplinary health care team. Lack of
awareness of specific guidelines can occur even though SSI outcomes are considered
to be important and major determinants of health care outcomes.93 Local regional cam-
paigns to improve compliance with these measures are also resource-intensive and
can be associated with marginal improvement in both compliance and outcomes.94

THERAPY

The general principle of SSI therapy remains control of the source of infection. For
superficial SSI, the standard management remains the use of incision and
 Surgical Site Infections 1257

drainage.62,95 The wound should be sufficiently sized to promote adequate drainage.

A variety of local wound care options are available, with the simplest being saline-
soaked cotton gauze dressings.62 For uncomplicated superficial SSIs, simple incision
and drainage, with local wound care, are appropriate, with no antibiotic therapy
required.96,97
Identification of deep SSI or complicated skin and soft tissue infection requires
adequate clinical suspicion. The presence of systemic features (eg, fever or leukocy-
tosis) with an absence of local signs of wound infection should raise suspicion for or-
gan/space SSI, or for an infection arising from an alternate site. In addition,
consideration should be made for antibiotic therapy in SSIs in patients with systemic
features, or widening erythema (>5 cm in diameter).97 Direct clinical examination
should follow to ensure an appropriate clinical response, with consideration of alterna-
tive diagnoses, if atypical features were to appear.
For more complicated skin and soft tissue infections, antibiotic therapy is appro-
priate, particularly in patients demonstrating signs of systemic shock. The principle
of source control remains important, with the appropriate selection of antibiotics
based on the type of surgical procedure performed, and the expected microbial
causes for the infection.62,95 As highlighted earlier, the growing impact of MDR organ-
isms will greatly increase the difficulty of treatment of SSIs. Effective prevention will
help to limit the potential impact of increasing resistance.

THE ECONOMIC AND QUALITY OF CARE IMPACT OF SURGICAL SITE INFECTIONS

The economic costs of SSIs are significant because of the volumes of cases that are
seen, with an annual 2.7 million operative procedures performed in the United States.5
Even with a conservative estimate of more than 290,000 cases of SSI,7 there is a sub-
stantial economic cost to the management of SSI. There is a wide variance in esti-
mates of the attributable costs of SSI infection that depends heavily on the type of
surgical procedure and the geographic region studied.98 There is additional confound-
ing of the economic cost estimates due the lack of risk stratification of patient popu-
lations studied, and methods of cost summation. The estimates vary from $3937 per
infection (Canadian tertiary care hospital)99 to about $20,000 per infection (American
orthopedic surgery population).100 These analyses may underestimate the economic
impact, through a combination of underestimation of surgical infection rates, and
the costs of the worst manifestations of SSI, such as organ/space SSI with accompa-
nying sepsis and septic shock, which can exceed $22,100 per case.101
The rates of SSI are increasingly being used as outcome and surrogate measures
for examining the quality of surgical care. The National Surgical Infection Prevention
Project was developed in 2003 with the goal to standardize quality improvement mea-
sure to decrease the incidence of SSI in major surgical procedures nationally.64 This
project has now transitioned to the Surgical Care Improvement Project (SCIP) in
2005, which included the SSI measures (Table 4) and additional performance mea-
sures of cardiac, respiratory, and thromboembolic complications.
In some countries these quality indicators have become pay-performance mea-
sures. For example, in the United States, the Centers for Medicare and Medicaid Ser-
vices linked Medicare payments to hospitals on their compliance to performance
indicators.102 The 2014 hospital payment rule finalized the general framework for
the Hospital-Acquired Condition Reduction Program to be implemented in 2015.103
The rule updated measures and financial incentives with the following areas related
to SSI: postoperative sepsis rate, wound dehiscence rate, central lineassociated
bloodstream infection, and catheter-associated urinary tract infection. The 2 new
1258 Young & Khadaroo

Table 4
Surgical care improvement project surgical site infection performance measures

SCIP INF-1 Prophylactic antibiotic received within 1 h before surgical incision

SCIP INF-2 Proper prophylactic antibiotic selected
SCIP INF-3 Prophylactic antibiotics discontinued within 24 h after surgery end time
SCIP INF-4 Cardiac surgery patients with controlled 6 AM postoperative blood glucose
measurement
SCIP INF-6 Appropriate hair removal
SCIP INF-9 Urinary catheter removed on postoperative day 1 or 2
SCIP INF-10 Appropriate perioperative temperature management

measures added of health careassociated infections were hospital-onset MRSA

bacteremia and Clostridium difficile.103
There have been conflicting results with studies examining the compliance of the
SCIP and the effect on SSI rates. Some studies have shown significantly lower SSI
rates in hospital groups with higher compliance rates with 2 specific SCIP measures
(appropriate antibiotic timing and antibiotic selection).104 Another study showed if at
least 2 of the 7 (see Table 3) measures were done there was a significant decrease
in the SSI rate; however, compliance of just one of the SCIP did not result in benefit.105
Although other studies have shown that adherence to multiple SCIP measures did not
correlate with a decrease of SSI,106,107 these studies demonstrate it is more than just
compliance to specific metric that influences outcome in SSI. The emphasis cannot be
only on adherence reporting but instead focused on a culture of safety and quality
within the team.

SUMMARY

SSIs remain a very important component of patient outcome, contributing to substan-

tial patient morbidity. From a historical perspective, there has been a significant
improvement in postsurgical outcomes, but these incremental gains have slowed in
the recent decades. The translation of basic and clinical research has expanded the
complexity of evidence-based guidelines for SSI prevention. The importance of SSI
prevention has been heightened because of its association with institutional and
regulatory quality control measures. Sustained research in multiple aspects of SSI
prevention needs to continue to realize further gains in SSI prevention. A multidisci-
plinary and multifaceted approach to SSI is absolutely necessary to continue to
improve these critical outcomes of surgery.

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